IL-4 Engagement of the Type I IL-4 Receptor Complex Enhances Mouse Eosinophil Migration to Eotaxin-1 In VitroReport as inadecuate




IL-4 Engagement of the Type I IL-4 Receptor Complex Enhances Mouse Eosinophil Migration to Eotaxin-1 In Vitro - Download this document for free, or read online. Document in PDF available to download.

Background

Previous work from our laboratory demonstrated that IL-4Rα expression on a myeloid cell type was responsible for enhancement of Th2-driven eosinophilic inflammation in a mouse model of allergic lung inflammation. Subsequently, we have shown that IL-4 signaling through type I IL-4 receptors on monocytes-macrophages strongly induced activation of the IRS-2 pathway and a subset of genes characteristic of alternatively activated macrophages. The direct effects of IL-4 and IL-13 on mouse eosinophils are not clear. The goal of this study was determine the effect of IL-4 and IL-13 on mouse eosinophil function.

Methods

Standard Transwell chemotaxis assay was used to assay migration of mouse eosinophils and signal transduction was assessed by Western blotting.

Results

Here we determined that i mouse eosinophils express both type I and type II IL-4 receptors, ii in contrast to human eosinophils, mouse eosinophils do not chemotax to IL-4 or IL-13 although iii pre-treatment with IL-4 but not IL-13 enhanced migration to eotaxin-1. This IL-4-mediated enhancement was dependent on type I IL-4 receptor expression: γC-deficient eosinophils did not show enhancement of migratory capacity when pre-treated with IL-4. In addition, mouse eosinophils responded to IL-4 with the robust tyrosine phosphorylation of STAT6 and IRS-2, while IL-13-induced responses were considerably weaker.

Conclusions

The presence of IL-4 in combination with eotaxin-1 in the allergic inflammatory milieu could potentiate infiltration of eosinophils into the lungs. Therapies that block IL-4 and chemokine receptors on eosinophils might be more effective clinically in reducing eosinophilic lung inflammation.



Author: Nicola M. Heller, William M. Gwinn, Raymond P. Donnelly, Stephanie L. Constant, Achsah D. Keegan

Source: http://plos.srce.hr/



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